The primary objective of this project is to provide a broad base of information on the expected responses of both normal and tumor tissues following exposure to negative pi mesons (pions), such that clinical trials of pion radiotherapy for patients with extensive cancer (which may include regional metastases) can be designed most effectively. These studies are being conducted jointly by the University of New Mexico Cancer Research and Treatment Center and the Los Alamos Scientific Laboratory. Sub-objectives are: a. Continue to develop the pion channel and associated hardware and to understand the physical characteristics of the beam, to achieve prescribed dose distributions in a treatment volume of arbitrary size and location, with minimum damage to surrounding normal tissue. b. Continue to develop, test, and apply methods of pion dosimetry essential to the radiobiology experiments, which will logically carry over into the early pilot trials and subsequent clinical trials of pion radiotherapy. c. Continue to employ appropriate quantitative cellular radiobiology techniques to establish the relative biological effectiveness (RBE), oxygen enhancement ratio (OER), and effects of dose fractionation of pions. d. Continue to observe in appropriate experimental animals early and late responses and radiopathology of normal and tumor tissues exposed to various segments of the pion beam to assess acute effects and delayed sequaelae as a function of dose and exposure conditions. e. Perform such radiobiological and physics experiments as may be necessary after the start of clinical trials.